In the lung, several enzyme systems including monooxygenase activity have been found to be localized within discrete cell populations. Consequently, several pulmonary toxins are particularly damaging to only select cell-types. In order to study where reduced oxygen species such as superoxide or hydrogen peroxide are produced within the lung, a histochemical technique utilizing the heavy metal, cerium, has been investigated. Cerium reacts with superoxide/hydrogen peroxide to produce a precipitate that can be readily visualized by electron microscopy. The technique has been applied mainly in rat lung slices using nitrofurantoin or high oxygen tensions as a source of reduced oxygen. Recent studies have also used isolated perfused rat lung and isolated rat lung cells to investigate localized production of superoxide. Extensive studies using Ce/H2O2 in the presence of a range of antioxidant enzymes and superoxide traps were undertaken in order to characterize the interaction of cerium with reduced oxygen. The rate of this reaction was biphasic, pH-dependent and inhibited by ascorbic acid, superoxide dismutase and albumin but not by ethanol or mannitol. In rat lung slices, cerium-derived electron dense bodies were seen principally around the alveolar type II cells. These bodies were diminished in the presence of catalase but markedly increased by superoxide dismutase. Studies are presently underway to quantify the precipitated cerium under various conditions using X-ray analysis and labeled cerium.